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Arch Neurol. 2008 Mar;65(3):349-57. doi: 10.1001/archneurol.2007.66.

Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility and gene expression.

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  • 1Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

BACKGROUND:

Interferon (IFN) gamma (IFNG) allelic variants are associated with susceptibility to multiple sclerosis (MS) in men but not in women.

OBJECTIVES:

To conduct a high-density linkage disequilibrium association study of IFNG and the surrounding region for sex-associated MS susceptibility bias and to evaluate whether IFNG allelic variants associated with MS susceptibility are associated with expression.

DESIGN:

Genotype case-control study, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay expression analyses for IFN gamma.

SETTING:

Three independently ascertained populations from the Mayo Clinic, Rochester, Minnesota, Queen's University of Belfast, Belfast, Ireland, and University of Leuven, Leuven, Belgium.

PATIENTS:

For linkage disequilibrium, 861 patients with MS (293 men and 568 women) and 843 controls (340 men and 503 women) derived from the US (population-based) and the Northern Ireland and Belgium (clinic-based) cohorts were studied. For expression analyses, 50 US patients were selected to enrich for homozygotes and to achieve a balance between men and women.

INTERVENTIONS:

Twenty markers were genotyped over the 120-kilobase region harboring IFNG and the interleukin 26 gene (IL26).

MAIN OUTCOME MEASURES:

Expression of IFN gamma was evaluated by qPCR and enzyme-linked immunosorbent assay in stimulated peripheral blood mononuclear cells.

RESULTS:

Multiple markers were associated with MS susceptibility in men but not in women. The sex-specific susceptibility markers, of which rs2069727 was the strongest, were confined to IFNG. Carriers of rs2069727*G had higher expression than noncarriers. The effect of genotype in the qPCR experiments was also evident in men but not in women.

CONCLUSIONS:

IFNG is associated with sex bias in MS susceptibility and with expression of IFN gamma in MS. These observations add to a growing body of literature that implicates an interaction between sex and IFN gamma expression in a variety of disease states.

PMID:
18332247
[PubMed - indexed for MEDLINE]
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